Metabolism of prostaglandin E2 in the isolated perfused kidney of the rabbit |
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Authors: | Mark J.S. Miller Eric G. Spokas John C. McGiff |
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Affiliation: | New York Medical College, Department of Pharmacology, Valhalla, NY 10595, U.S.A. |
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Abstract: | In the Krebs-perfused rabbit isolated kidney, [3H]PGE2 (5 μCi, 165 Ci/mmole) was infused intra-arterially for 5 min; venous and urinary effluents were collected every 2 min for 20 min. Efflux of radioactive material peaked at 8 min and declined thereafter. The kidney retained 35% of the infused 3H. Samples were extracted for acidic lipids; PGE2, PGF2α and metabolites were separated by TLC and quantified by a radiometric method. Efflux of [3H]PGF2α into urinary and venous outflows increased progressively over the first 12 min and then plateaued for the remaining 4 min. By 12 min, conversion of [3H]PGE2 to [3H]PGF2α was 70 and 80% as determined by radiolabeled products recovered in the urinary and venous effluents respectively. Estimates of total conversion of [3H]PGE2 to [3H]PGF2α were 62 and 52% of the radiolabeled material exiting in the urinary and venous effluents respectively. The 15-keto and 13,14-dihydro-15-keto metabolites of [3H]PGF2α appeared in the urine but were not found in the venous outflow. We conclude that PGE-9-ketoreductase (PGE-9KRD) activity is high in the rabbit isolated perfused kidney. Further, the extent of conversion of PGE2 to PGF2α and metabolism of newly formed PGF2α may differ within the vascular and tubular compartments of the kidney. PGE-9KRD activity may be important in the regulation of renal vascular tone, compliance of veins, and salt and water balance. |
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Keywords: | Address correspondence to: Mark J.S. Miller Ph.D. Department of Pharmacology New York Medical College Valhalla NY 10595 U.S.A. |
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